tbuckley/cabot-search huggingface dataset:
STRIVE-02: A first-in-human phase 1 trial of systemic B7H3 CAR T cells for children and young adults with relapsed/refractory solid tumors.
Authors: Navin R. Pinto, Catherine Michelle Albert, Mallory Taylor, Ashley Wilson, Stephanie Rawlings-Rhea, Wenjun Huang, Kristy Seidel, Prabha Narayanaswany, Vicky Wu, Christopher Brown, Nicholas A. Vitanza, Rimas Orentas, Rebecca Alice Gardner, Michael C. Jensen, Julie R. Park
Journal: Journal of Clinical Oncology (2022)

10011 Background: B7H3 (CD276) has limited expression in normal tissues and high cell-surface expression in pediatric solid malignancies providing rationale for immunologic therapeutic targeting. We present a first-in-human experience of B7H3 chimeric antigen receptor T cells (CAR-T) for children and young adults (CYA) with relapsed or refractory solid tumors (R/RST). Methods: CYA patients with R/RST were enrolled onto a Phase 1 trial (NCT04483778) to examine the safety of autologous T cells genetically modified to express scFV-IgG4hinge-CD28tm-4-1BB-zeta B7H3-specific CAR with the methotrexate resistance/selection cassette DHFRdm and the tracking/suicide construct EGFRt. All patients received lymphodepleting fludarabine and cyclophosphamide prior to infusion of cryopreserved CAR-T at the prescribed dose level. The maximal tolerated dose or biologically effective dose (BED) was determined based upon observed toxicity through day 28 from initial CAR-T infusion and using a 3+3 statistical design. Results: Sixteen subjects (age 11-24, median 17 years) enrolled and received dose level (DL) 1 (0.5 x 10 6 CAR-T/kg, n = 3) or DL2 (1 x 10 6 CAR-T cells/kg, n = 6). No dose limiting toxicity was observed following first infusion, most common toxicities were fatigue and cytokine release syndrome (CRS) (n = 2, maximum CTCAE grade 2). Maximum circulating CAR-T expansion on first infusion was 4.98 cells/uL (range 0.23-4.98 cells/uL) with median persistence of 28 days (range 14-90). Best overall response of Stable Disease was observed in 3 of the 9 subjects infused. Given observed expansion and persistence, DL2 was determined to be the BED. A second infusion at DL2 in one subject demonstrated CAR T expansion to 1590 cells/uL (86% of circulating CD3 cells) with CTCAE grade 2 CRS and transient dose limiting CTCAE grade 4 liver enzyme elevation. A partial metabolic response on FDG-PET by PERCIST criteria was observed in this subject at Day 28. Conclusions: B7H3 CAR T cells are safe and demonstrate anti-tumor activity in CYA with R/RST. CAR-T cell expansion and persistence may be necessary to achieve objective responses. STRIvE-02 Arm B will explore dual expression of CD19 CAR with B7H3 CAR, using lymphocytic CD19 expression to drive CAR expansion and persistence. Clinical trial information: NCT04483778.
Clinical and Financial Outcomes Associated With a Workplace Mental Health Program Before and During the COVID-19 Pandemic
Authors: Julia Bondar, Cecina Babich Morrow, Ralitza Gueorguieva, Millard Brown, Matt Hawrilenko, John H. Krystal, Philip R. Corlett, Adam M. Chekroud
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Investment in workplace wellness programs is increasing despite concerns about lack of clinical benefit and return on investment (ROI). In contrast, outcomes from workplace mental health programs, which treat mental health difficulties more directly, remain mostly unknown. <h3>Objective</h3> To determine whether participation in an employer-sponsored mental health benefit was associated with improvements in depression and anxiety, workplace productivity, and ROI as well as to examine factors associated with clinical improvement. <h3>Design, Setting, and Participants</h3> This cohort study included participants in a US workplace mental health program implemented by 66 employers across 40 states from January 1, 2018, to January 1, 2021. Participants were employees who enrolled in the mental health benefit program and had at least moderate anxiety or depression, at least 1 appointment, and at least 2 outcome assessments. <h3>Intervention</h3> A digital platform that screened individuals for common mental health conditions and provided access to self-guided digital content, care navigation, and video and in-person psychotherapy and/or medication management. <h3>Main Outcomes and Measures</h3> Primary outcomes were the Patient Health Questionnaire-9 for depression (range, 0-27) score and the Generalized Anxiety Disorder 7-item scale (range, 0-21) score. The ROI was calculated by comparing the cost of treatment to salary costs for time out of the workplace due to mental health symptoms, measured with the Sheehan Disability Scale. Data were collected through 6 months of follow-up and analyzed using mixed-effects regression. <h3>Results</h3> A total of 1132 participants (520 of 724 who reported gender [71.8%] were female; mean [SD] age, 32.9 [8.8] years) were included. Participants reported improvements from pretreatment to posttreatment in depression (<i>b</i> = −6.34; 95% CI, −6.76 to −5.91; Cohen<i>d</i> = −1.11; 95% CI, −1.18 to −1.03) and anxiety (<i>b</i> = −6.28; 95% CI, −6.77 to −5.91; Cohen<i>d</i> = −1.21; 95% CI, −1.30 to −1.13). Symptom change per log-day of treatment was similar post–COVID-19 vs pre–COVID-19 for depression (<i>b</i> = 0.14; 95% CI, −0.10 to 0.38) and anxiety (<i>b</i> = 0.08; 95% CI, −0.22 to 0.38). Workplace salary savings at 6 months at the federal median wage was US $3440 (95% CI, $2730-$4151) with positive ROI across all wage groups. <h3>Conclusions and Relevance</h3> Results of this cohort study suggest that an employer-sponsored workplace mental health program was associated with large clinical effect sizes for employees and positive financial ROI for employers.
Placebo and nocebo response in the medical treatment of adults with nocturia: A systematic review and meta-analysis
Authors: H. Mostafaei, K. Mori, B. Pradere, T. Kawada, R. Sari Motlagh, T. Yanagisawa, F. Quhal, E. Laukhtina, P. Rajwa, A. Aydh, F. König, M. Pallauf, H. Salehi-Pourmehr, S. Hajebrahimi, S.F. Shariat
Journal: European Urology (2022)
Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522.
Authors: Lajos Pusztai, Carsten Denkert, Joyce O'Shaughnessy, Javier Cortes, Rebecca Alexandra Dent, Heather L. McArthur, Sherko Kuemmel, Jonas C. S. Bergh, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Michael Untch, Peter A. Fasching, Fatima Cardoso, Yalin Zhu, Wilbur Pan, Konstantinos Tryfonidis, Peter Schmid
Journal: Journal of Clinical Oncology (2022)

503 Background: KEYNOTE-522 (NCT03036488) tested the benefit from adding pembrolizumab (pembro) to chemotherapy (chemo) in patients (pts) with early TNBC. The primary results showed statistically significant and clinically meaningful improvements in pCR and EFS with pembro.Prior studies have shown the prognostic value of the residual cancer burden (RCB) method to quantify the extent of residual disease after neoadjuvant chemo. In this exploratory analysis, we assessed EFS by RCB in KEYNOTE-522. Methods: 1174 pts with previously untreated, nonmetastatic, stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2:1 to pembro 200 mg Q3W or placebo (pbo) given with 4 cycles of paclitaxel + carboplatin, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR and EFS. RCB was assessed by the local pathologist at the time of surgery. The association between RCB categories (RCB-0, -1, -2, -3, corresponding to increasingly larger residual cancer) and EFS was assessed based on a Cox regression model with treatment as a covariate. Results: Median follow-up was 39.1 months at data cutoff (23 MAR 2021). Pembro shifted RCB to lower categories across the entire spectrum (Table). The HRs (95% CI) for EFS were 0.70 (0.38 - 1.31) for RCB-0 (equivalent to pCR), 0.92 (0.39 - 2.20) for RCB-1, 0.52 (0.32 - 0.82) for RCB-2, and 1.24 (0.69 - 2.23) for RCB-3. The most common EFS event in both arms was distant recurrence, which occurred in fewer pts in the pembro arm in all RCB categories. Conclusions: Increased RCB score was associated with worse EFS. Pts with residual disease had lower RCB values in the pembro arm, including fewer pts with RCB-3. Pembro + chemo prolonged EFS vs chemo alone in the RCB-0, -1, and -2 categories; the small sample size limits interpretation in the RCB-3 category. The small subset of pts with extensive residual disease (RCB-3) in both arms, 5.1% and 6.7%, respectively, had a poor prognosis. These results highlight the importance of neoadjuvant treatment with pembro for improving survival in pts with early TNBC, and identified a subset of pts for whom additional therapies will be needed. Clinical trial information: NCT03036488. [Table: see text]
PATH-12. A new powerful tool to simultaneously deliver DNA methylation profile and driver fusions detection based on Nanopore Sequencing
Authors: Mathilde Filser, Abderaouf Hamza, Elodie Girard, Nicolas Servant, Victor Renault, Kevin Merchadou, Christine Bourneix, Pascale Varlet, Emmanuelle Uro-Coste, Arnault Tauziède-Espariat, Francois Doz, Franck Bourdeaut, Olivier Delattre, Julien Masliah-Planchon
Journal: Neuro-Oncology (2022)

Abstract The fast advances in molecular biology have led to the discovery of new genetic and epigenetic driver events that play a key role in the pathogenesis of central nervous system (CNS) tumors. These data showed the importance of molecular biology, and in particular methylation profiling and fusion detection, to complete the histological examination. Exploring all these complex genomic and epigenomic alterations with the technologies implemented in the routine diagnosis requires massive laboratory equipment. In addition, it could take weeks before getting data that could be important to adapt the diagnosis, prognosis, and to ultimately guide the treatment’s choice. We describe the innovative potential of a nanopore sequencing device to obtain fast and multiple information to characterize CNS tumors. Adaptive-sampling is a software-controlled enrichment unique method that allows simultaneous methylation profiling, copy number landscape assessment, and fusion gene detection. Thereby, this technology brings comprehensive molecular information that could be very important for CNS tumor classification in a very short delay (below one week) and with a relative low cost compared to the combined other molecular analysis needed to get the same information. We report ten cases of diverse CNS tumors with already known oncogenic structural variants such as YAP1-MAMLD1 fused ependymoma, CNS neuroblastoma with FOXR2 activation, CNS high-grade neuroepithelial tumor with BCOR and MEN1 alteration, and atypical teratoid rhabdoid tumors (ATRT). For these tumors, using adaptive sampling with the nanopore sequencing, we were able to detect fusion genes as driver events, while obtaining at the same time the methylation profile to corroborate the tumor classification. Our results with this combined approach, never described before, demonstrate its feasibility as a new extremely powerful tool and show remarkable perspectives for this technology to bring a fast and comprehensive tumor molecular characterization.
The expression of aryl hydrocarbon receptor predicts responses to anti-PD-1 antibodies in non-small cell lung cancer.
Authors: Si-Chong Han, Yaning Yang, Gui-Zhen Wang, Wenfeng Fang, Li Zhang, Yan Wang, Guang-Biao Zhou
Journal: Journal of Clinical Oncology (2022)

2628 Background: Blockade of programmed cell death receptor 1 (PD-1) by antibodies such as pembrolizumab has revolutionized treatment for patients with non-small cell lung cancer (NSCLC). However, a significant number of patients achieve only marginal benefit. The predictive abilities of the frequently used biomarkers, including programmed cell death 1 ligand (PD-L1) and tumor mutation burden (TMB), are yet limited, highlighting the urgent need for more reliable biomarkers. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that controls the transcription of its targets including PD-L1. Whether AhR could be used as a predictive biomarker for response to PD-1 blockade immunotherapy in NSCLC warrants further investigation. Methods: We collected formalin-fixed, paraffin-embedded (FFPE) slides from 104 NSCLC patients before PD-1 blockade immunotherapy treatment, who had sufficient follow-up data for progression-free survival (PFS), and detected the expression of nuclear localized AhR (AhR N ) and membrane localized PD-L1 (PD-L1 M ) with multiplex immunohistochemistry (mIHC). H-score was applied to characterize the specific value with the following formula [1 × (% cells intensity =1) + 2 × (% cells intensity = 2) + 3 × (% cells intensity = 3)]. Survival curve for each group was estimated by the Kaplan–Meier method and log-rank test. The diagnostic performance was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), which was calculated based on the Wilcoxon rank-sum test. All statistical tests were two-sided and P values less than 0.05 were considered statistically significant. Results: Both AhR N and PD-L1 M could distinguish responders from non-responders, and patients with higher H-score had longer PFS than those with lower H score. The AUC of AhR N was 0.804 (95 % CI: 0.721-0.881), higher than that of PD-L1 M (0.714; 95 % CI: 0.618-0.811) and AhR N +PD-L1 M (0.743; 95 % CI: 0.649-0.837), indicating AhR N might show better predictive capacity to the efficacy of PD-1 blockade immunotherapy than PD-L1 M . Besides, AhR N exhibited the most significant accuracy in prognosis prediction, since the hazard ratio (HR) of AhR N was 0.1529 (95 % CI: 0.07704-0.3033, P&lt;0.0001), significantly higher than that of PD-L1 M [HR:0.283 (95 % CI: 0.1525-0.525, P&lt;0.0001)] and AhR N +PD-L1 M [HR: 0.2456 (95 % CI: 0.1309-0.4607, P&lt;0.0001)]. Yet, among the 54 smokers, AhR N +PD-L1 M was the best classifier for the efficacy of immunotherapy, of which the AUC was 0.8937 (95 % CI: 0.816-0.971) and HR was infinitely approaching 0 ( P&lt;0.0001). Conclusions: AhR might be a reliable predictive biomarker for PD-1 blockade immunotherapy in NSCLCs.
Efficacy of Gemcitabine in recurrent meningioma: A phase II study.
Authors: Devanshee Shah, Nandini Sharrel Menon, Ameya Puranik, Amit Choudhary, Vijay Maruti Patil, Shruti Pathak, Zoya Peelay
Journal: Journal of Clinical Oncology (2022)

e14044 Background: Systemic therapy has a limited role in meningiomas. There is in-vivo and in-vitro data that gemcitabine can potentially be useful in meningiomas. We did a phase II study with the primary objective of studying the 6-month progression-free survival (PFS) of gemcitabine in meningiomas. Methods: This was a single-arm prospective phase II study. Adult patients with recurrent meningiomas who were not eligible for local therapies with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 with normal organ and marrow function were included in this study. Patients who had received any chemotherapy within the last three weeks or on any other investigational agents were excluded. All patients received gemcitabine 1000 mg/m2 administered intravenously over 30 minutes on day 1, day 8 and day 15 every 4 weeks until disease progression or development of intolerable side effects. The response was assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. The adverse events were recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The primary objective of this study was to assess the 6-months progression-free survival (PFS). The 6-months progression-free survival (PFS) of 50% or more was considered sufficient to warrant further studies. Results: Nine patients were recruited in this study. The median age of the patient was 56 years(24-73). The m: f ratio was 2:3. All patients had undergone previous surgeries and 8 patients had undergone previous radiotherapy. The median number of cycles of gemcitabine was 3. Any grade toxicity was observed in all patients. Grade 3 and above adverse events were not observed. The two commonest adverse events noted were anaemia in 7 (77.8%) patients and vomiting in 2 (22.2) patients. The best response was stable disease (SD) in 3 patients (33.4%) and progressive disease (PD) in 6 (66.6%) patients. At a median follow up of 18.8 months, the 6-months progression-free survival (PFS) was 33.3% (95%CI 7.8-62.3). The 1-year overall survival (OS) was 66.7 % (95%CI 28.2-87.8). Conclusions: Gemcitabine failed to meet the prespecified endpoint of 6-month PFS and does not warrant any further investigation in this setting. Clinical trial information: CTRI/2019/02/017499.
Impact of readmission for patients with cancer in a public health system.
Authors: Cassio Murilo Trovo Hidalgo Filho, Felippe Lazar Neto, Joao Wilson Da Rocha, Renata Colombo Bonadio, Paulo Marcelo Hoff
Journal: Journal of Clinical Oncology (2022)

e18633 Background: Patients with cancer have high mortality during hospitalization and poor prognosis after discharge. However, most evidence comes from developed countries where early diagnosis is common and a higher number of treatment options are available. In addition, socioeconomic disparity is also known to impact on cancer prognosis. We aimed to investigate the impact of hospitalizations, early readmissions, and Human Development Index (HDI) among cancer patients in a public tertiary hospital in Brazil. Methods: A retrospective study was conducted including patients admitted at a Brazilian tertiary cancer center from February 1st to November 30th of 2021. Data was collected from patients' electronic health records. COVID-19 diagnosed patients were excluded. We evaluated 7-day and 30-day readmission rate, and post-discharge survival. We retrieved patients' home address region HDI from the latest Brazilian Census and investigated if it would affect hospitalization and post-discharge outcomes. Overall survival (OS) after discharge was compared between groups with log-rank test and categorical variables proportions with chi-square test. Results: A total of 3711 patients were included during the period. The median age was 64 years (IQR 53-72); nearly half were female (51%). The most common cancer diagnosis was breast cancer (538, 15%) followed by prostate (308, 8.4%), colon (298, 8.1%) and lung (269, 7.3%). The median hospitalization length was 6 days (IQR 4-11). The overall in-hospital mortality rate was 20% (n = 734). Patients initially admitted to the Intensive Care Unit (ICU) had a higher mortality compared to wards (44% vs 17%, p &lt; 0.001). Of those discharged, 9.9% and 28% of the patients were readmitted within 7 and 30 days, respectively. The median overall survival (mOS) of the discharged patients was 182 days (95% CI 160-201 days). Early readmission within 7 and 30 days were associated with poorer overall survival after discharge (Table, p &lt; 0.001). We have not found any association between the HDI and in-hospital mortality, rate of readmissions or overall survival after discharge. Conclusions: Early readmission is an important prognostic factor and should be taken into consideration when discussing post-discharge treatment objectives. HDI does not seem to affect neither hospitalization nor survival outcomes in a publicly funded cancer center.[Table: see text]
Impact of social media on the emotional health and burnout of pediatric and adult oncology professionals: A SWOG and COG survey.
Authors: Scott Moerdler, Maura Meredith Barry, Elizabeth Henry, Tiffany Lin Lucas, Ariela Lucy Marshall, Don S. Dizon
Journal: Journal of Clinical Oncology (2022)

11013 Background: Social media (SoMe) engagement is common in oncology, especially for patients and support groups, allowing for education and support. However the impact on oncology professionals remains unknown. The purpose of this study was to evaluate professional SoMe use and its potential associations with wellbeing and burnout. Methods: An electronic survey was developed and piloted by pediatric and adult oncologists. Questions included demographics, details of SoMe use, and emotional health assessments including a 2-item burnout questionnaire. The survey was distributed to all members of SWOG Cancer Research Network and Children’s Oncology Group via Qualtrics. Data was analyzed as of 2/6/2022. Results: The initial survey demographic and emotional health questions were completed by 1558 individuals. Of these, 1069 (68%) reported not using SoMe professionally, while 489 (31%) did. SoMe engagers were primarily female, born 1976–1984, attendings, from academic institutions, and balanced across adult and pediatrics (Table). Among those who use SoMe professionally, 54% (267/489) reported burnout, compared to 66% (701/1069) in the non-SoMe group (p = 0.0001). Remaining emotional health outcomes were similar between groups: choosing this job/career again, time for personal/family life, and career satisfaction (p &gt; 0.1 for all). An additional section on the impact of SoMe on emotional health was completed by 473 SoMe engagers. While 49% (233/473) reported that SoMe has no impact on burnout, 18% (86/473) felt that SoMe helps alleviate burnout. SoMe use was reported to have somewhat/extremely positive impact on wellness (defined as physical, mental, emotional, spiritual wellness) by 28% (131/473). Networking and recognized shared experiences were the top areas of SoMe that improved wellness. Close to half (208/473, 44%) responded that SoMe does not negatively impact wellness. Professional anxiety, amount of time spent online, and keeping up to maintain an online presence were the most frequently noted aspects that negatively impact wellness. Nearly half (232/473, 49%) somewhat/strongly agree that SoMe provides a sense of community. One limitation includes distribution to engaged cooperative group members which may impact results. Conclusions: This analysis suggests that social media engagement might help provide a positive impact on the wellness and reduce burnout among oncology professionals. We hope to further explore themes with qualitative interviews to better understand the impact of SoMe on our emotional health. Our goal is to develop educational interventions based on these salient positive and negative factors. [Table: see text]